Criteria for optimal electrical resynchronization during fusion pacing

ABSTRACT

Generally, the disclosure is directed one or more methods or systems of cardiac pacing employing a plurality of left ventricular electrodes. Pacing using a first one of the left ventricular electrodes and measuring activation times at other ones of the left and right ventricular electrodes. Pacing using a second one of the ventricular electrodes and measuring activation times at other ones of the left ventricular electrodes. Employing weighted sums of the measured activation times to measure a fusion index and select one of the left ventricular electrodes for delivery of subsequent pacing pulses based on comparing fusion indices during pacing from different LV electrodes. One or more embodiments use the same fusion index to select an optimal A-V delay by comparing fusion indices during pacing with different A-V delays at resting atrial rates as well as rates above the resting rate.

FIELD

The present disclosure relates to implantable medical devices (IMDs),and, more particularly, to selecting an optimal left ventricularelectrode on a medical electrical lead extending from an IMD to delivercardiac therapy.

BACKGROUND

Implantable medical devices (IMD) are capable of utilizing pacingtherapies, such as cardiac resynchronization therapy (CRT), to maintainhemodynamic benefits to patients. Fusion pacing is a form of CRTtherapy. Fusion pacing reduces the power consumed by an implantablemedical device since only one ventricle is paced in coordination withthe other ventricle's intrinsic activation. For example, the leftventricle (LV) can be paced in coordination with the intrinsic rightventricle (RV) activation or vice versa. Recent developments in fusionpacing have been described in printed publications. For example, USPatent Publication 2011/0137639 by Ryu et al. discloses that the optimalleft ventricle electrode is selected based upon conduction velocities.Another U.S. Pat. No. 7,917,214 to Gill et al. discloses that theoptimal left ventricle electrode is selected based upon activation timesand activation recovery interval dispersions. It is desirable to developadditional methods and systems to optimize fusion pacing.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of an exemplary system including anexemplary implantable medical device (IMD).

FIG. 2 is a schematic diagram of the exemplary IMD of FIG. 1.

FIGS. 3-3A are schematic diagrams of an enlarged view of a distal end ofa medical electrical lead disposed in the left ventricle.

FIG. 4 is a block diagram of an exemplary IMD, e.g., the IMD of FIGS.1-2.

FIG. 5 is a general flow chart of an exemplary method that involvesdetermining a weighted electrical dyssynchrony for selecting an optimalleft ventricle electrode to pace a left ventricle.

FIG. 6A is a general flow chart of an exemplary method that involvesselecting an optimal electrode to pace a ventricle.

FIG. 6B is a general flow chart of another exemplary method thatinvolves selecting an optimal electrode to pace a ventricle.

FIG. 7 is a general flow chart of an exemplary method that involvesdetermining a weighted electrical dyssynchrony for selecting an optimalA-V delay.

FIG. 8 depicts a ventricular electrogram that includes ventricularactivations times.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

In the following detailed description of illustrative embodiments,reference is made to the accompanying figures of the drawing which forma part hereof, and in which are shown, by way of illustration, specificembodiments which may be practiced. It is to be understood that otherembodiments may be utilized and structural changes may be made withoutdeparting from (e.g., still falling within) the scope of the disclosurepresented hereby.

As described herein, a physician implanting a medical device can usecriteria, stored in a programmer, to automatically select optimizedlocation(s) and/or parameters for delivery of cardiac resynchronizationtherapy (CRT) through fusion pacing. For example, in one or moreembodiments, criteria can be used to determine an optimal leftventricular (LV) electrode from which electrical stimuli is delivered tothe left ventricle. After the optimal LV electrode has been selected,other criteria can be used to optimize an atrioventricular delay formaximal cardiac resynchronization. In one or more other embodiments,different criteria can be used to determine an optimal right ventricular(RV) electrode from which electrical stimuli is delivered to the rightventricle. After the optimal RV electrode has been selected, criteriacan be used to optimize an atrioventricular delay for maximal cardiacresynchronization. Implementation of teachings of this disclosure canpotentially improve CRT response in patients through fusion pacing. Forexample, heart failure patients with stable intrinsic A-V conduction andintraventricular conduction disorder (e.g. left bundle branch block,right bundle branch block) may have an improved response to CRT byimplementing features described herein.

Exemplary methods, devices, and systems are described with reference toFIGS. 1-8. It is appreciated that elements or processes from oneembodiment may be used in combination with elements or processes of theother embodiments. The possible embodiments of such methods, devices,and systems using combinations of features set forth herein is notlimited to the specific embodiments shown in the Figures and/ordescribed herein. Further, it will be recognized that the embodimentsdescribed herein may include many elements that are not necessarilyshown to scale. Still further, it will be recognized that timing of theprocesses and the size and shape of various elements herein may bemodified but still fall within the scope of the present disclosure,although certain timings, one or more shapes and/or sizes, or types ofelements, may be advantageous over others.

FIG. 1 is a conceptual diagram illustrating an exemplary therapy system10 that may be used to deliver fusion pacing therapy to a patient 14that may, but not necessarily, be a human. Fusion pacing typicallyinvolves left ventricle (LV) only pacing with an electrode on the LVmedical electrical lead in coordination with the intrinsic rightventricle (RV) activation. Alternatively, fusion pacing can involvepacing the RV with an electrode on the RV medical electrical lead incoordination with the intrinsic LV activation.

The therapy system 10 may include an implantable medical device 16(IMD), which may be coupled to leads 18, 20, 22 and a programmer 24. Forthe sake of brevity, programmer 24 includes a computer capable of thefunctions represented in FIG. 4 that are incorporated herein.

The IMD 16 may be, e.g., an implantable pacemaker, cardioverter, and/ordefibrillator, that provides electrical signals to the heart 12 of thepatient 14 via electrodes coupled to one or more of the leads 18, 20,22.

The leads 18, 20, 22 extend into the heart 12 of the patient 14 to senseelectrical activity of the heart 12 and/or to deliver electricalstimulation to the heart 12. In the example shown in FIG. 1, the rightventricular (RV) lead 18 extends through one or more veins (not shown),the superior vena cava (not shown), and the right atrium 26, and intothe right ventricle 28. The left ventricular coronary sinus lead 20extends through one or more veins, the vena cava, the right atrium 26,and into the coronary sinus 30 to a region adjacent to the free wall ofthe left ventricle (LV) 32 of the heart 12. The right atrial (RA) lead22 extends through one or more veins and the vena cava, and into theright atrium 26 of the heart 12.

The IMD 16 may sense, among other things, electrical signals attendantto the depolarization and repolarization of the heart 12 via electrodescoupled to at least one of the leads 18, 20, 22. In some examples, theIMD 16 provides pacing therapy (e.g., pacing pulses) to the heart 12based on the electrical signals sensed within the heart 12. The IMD 16may be operable to adjust one or more parameters associated with thepacing therapy such as, e.g., pulse width, amplitude, voltage, burstlength, etc. Further, the IMD 16 may be operable to use variouselectrode configurations to deliver pacing therapy, which may beunipolar or bipolar. The IMD 16 may also provide defibrillation therapyand/or cardioversion therapy via electrodes located on at least one ofthe leads 18, 20, 22. Further, the IMD 16 may detect arrhythmia of theheart 12, such as fibrillation of the ventricles 28, 32, and deliverdefibrillation therapy to the heart 12 in the form of electrical pulses.In some examples, IMD 16 may be programmed to deliver a progression oftherapies, e.g., pulses with increasing energy levels, until afibrillation of heart 12 is stopped.

In some examples, a programmer 24, which may be a handheld computingdevice or a computer workstation, may be used by a user, such as aphysician, technician, another clinician, and/or patient, to communicatewith the IMD 16 (e.g., to program the IMD 16). For example, the user mayinteract with the programmer 24 to retrieve information concerning oneor more detected or indicated faults associated within the IMD 16 and/orthe pacing therapy delivered therewith. The IMD 16 and the programmer 24may communicate via wireless communication using any techniques known inthe art. Examples of communication techniques may include, e.g., lowfrequency or radiofrequency (RF) telemetry, but other techniques arealso contemplated.

FIG. 2 is a conceptual diagram illustrating the IMD 16 and the leads 18,20, 22 of therapy system 10 of FIG. 1 in more detail. The leads 18, 20,22 may be electrically coupled to a therapy delivery module (e.g., fordelivery of pacing therapy), a sensing module (e.g., one or moreelectrodes to sense or monitor electrical activity of the heart 12 foruse in determining effectiveness of pacing therapy), and/or any othermodules of the IMD 16 via a connector block 34. In some examples, theproximal ends of the leads 18, 20, 22 may include electrical contactsthat electrically couple to respective electrical contacts within theconnector block 34 of the IMD 16. In addition, in some examples, theleads 18, 20, 22 may be mechanically coupled to the connector block 34with the aid of set screws, connection pins, or another suitablemechanical coupling mechanism.

Each of the leads 18, 20, 22 includes an elongated insulative lead body,which may carry a number of conductors (e.g., concentric coiledconductors, straight conductors, etc.) separated from one another byinsulation (e.g., tubular insulative sheaths). Exemplary leads that canbe useful for the present disclosure include U.S. Pat. No. 5,922,014,U.S. Pat. No. 5,628,778, U.S. Pat. Nos. 4,497,326, 5,443,492, U.S. Pat.No. 7,860,580 or US Patent Application 20090036947 filed Apr. 30, 2008such that electrodes are added and/or spaced apart in a manner similarto that disclosed in the figures of the present application, all oflisted patents and applications are incorporated by reference in theirentirety. Additional lead and electrode configurations that may beadapted for use with the present disclosure by adjusting lead shape,length, electrode number and/or electrode to effectively avoid phrenicnerve stimulation as described herein are generally disclosed in U.S.Pat. No. 7,031,777, U.S. Pat. No. 6,968,237, and US Publication No.2009/0270729, all of which are incorporated herein by reference in theirentirety. Moreover, U.S. Pat. No. 7,313,444, incorporated by reference,discloses a LV pacing lead such that the LV electrodes are about equallyspaced, which could also be used to implement the present disclosure.

In the illustrated example, bipolar or unipolar electrodes 40, 42 (alsoreferred to as RV electrodes) are located proximate to a distal end ofthe lead 18. Referring briefly to FIGS. 3-3A, the electrodes 44, 45, 46are located proximate to a distal end of the lead 20 and the bipolar orunipolar electrodes 56, 50 (FIG. 2) are located proximate to a distalend of the lead 22. Electrodes 44, 45, 46 and 47 can be bipolarelectrodes, unipolar electrodes or a combination of bipolar and unipolarelectrodes. Additionally, electrodes 44, 45, 46 and 47 have an electrodesurface area of about 5.3 mm² to about 5.8 mm². Electrodes 44, 45, 46,and 47 are also referred to as LV1 (electrode 1), LV2 (electrode 2), LV3(electrode 3), and LV4 (electrode 4), respectively. As shown, lead 20includes a proximal end 92 and a distal end 94. The distal end 94 isplaced in or near LV tissue. Skilled artisans appreciate that LVelectrodes (i.e. left ventricle electrode 1 (LV1) 44, left ventricleelectrode 2 (LV2) 45, left ventricle electrode 3 (LV3) 46, and leftventricle 4 (LV4) 47 etc.) on lead 20 can be spaced apart at variabledistances. For example, electrode 44 is a distance 96 a (e.g. about 21mm) away from electrode 45, electrodes 45 and 46 are spaced a distance96 b (e.g. about 1.3 mm to about 1.5 mm) away from each other, andelectrodes 46 and 47 are spaced a distance 96 c (e.g. 20 mm to about 21mm) away from each other.

The electrodes 40, 44, 45, 46, 47, 48 may take the form of ringelectrodes, and the electrodes 42, 47, 50 may take the form ofextendable helix tip electrodes mounted retractably within theinsulative electrode heads 52, 54, 56, respectively. Each of theelectrodes 40, 42, 44, 45, 46, 47, 48, 50 may be electrically coupled toa respective one of the conductors (e.g., coiled and/or straight) withinthe lead body of its associated lead 18, 20, 22, and thereby coupled torespective ones of the electrical contacts on the proximal end of theleads 18, 20, 22. The electrodes 40, 42, 44, 45, 46, 47, 48, 50 mayfurther be used to sense electrical signals attendant to thedepolarization and repolarization of the heart 12. The electricalsignals are conducted to the IMD 16 via the respective leads 18, 20, 22.In some examples, the IMD 16 may also deliver pacing pulses via theelectrodes 40, 42, 44, 45, 46, 47, 48, 50 to cause depolarization ofcardiac tissue of the patient's heart 12. In some examples, asillustrated in FIG. 2, the IMD 16 includes one or more housingelectrodes, such as housing electrode 58, which may be formed integrallywith an outer surface of a housing 60 (e.g., hermetically-sealedhousing) of the IMD 16 or otherwise coupled to the housing 60. Any ofthe electrodes 40, 42, 44, 45, 46, 47, 48 and 50 may be used forunipolar sensing or pacing in combination with housing electrode 58.Further, any of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, which arenot being used to deliver pacing therapy, may be used to senseelectrical activity during pacing therapy (e.g., for use in determiningelectrical activation times). Electrical activation time can be used todetermine whether fusion pacing produces effective contraction of theheart based on metrics of electrical dyssynchrony derived from theventricular activation times.

Electrical activation time or local electrical activity is determinedrelative to timing of a fiducial, an indicator of a global cardiac event(e.g. timing of contraction of a chamber of the heart, timing of pacingof a chamber of the heart, etc.) For example, the fiducial may be theonset of the QRS waves (e.g. minimum values, minimum slopes, maximumslopes), zero crossings, threshold crossings, most negative slope, etc.of a near or far-field EGM), onset of application of a pacing electricalstimulus, or the like. After a fiducial point is selected, activationtimes are determined by measuring time between the delivery of pacingstimulus using a pacing electrode and the appropriate fiducial pointwith the electrical activity sensed by a non-pacing electrode. Thedevice delivering the pacing signal may include appropriate electronicsto track and mark the timing of the pacing signal, which marked ortracked time may be used for purposes of determining local activationtime and electrical dispersion as discussed above. The device thatdelivers the pacing signal may be a device configured for deliveringCRT.

As described in further detail with reference to FIG. 4, the housing 60may enclose a therapy delivery module that may include a stimulationgenerator for generating cardiac pacing pulses and defibrillation orcardioversion shocks, as well as a sensing module for monitoring thepatient's heart rhythm. Cardiac pacing involves delivering electricalpacing pulses to the patient's heart, e.g., to maintain the patient'sheart beat (e.g., to regulate a patient's heart beat, to improve and/ormaintain a patient's hemodynamic efficiency, etc.). Cardiac pacinginvolves delivering electrical pacing pulses ranging from about 0.25volts to about 8 volts and more preferably, between 2-3 volts.

The leads 18, 20, 22 may also include elongated electrodes 62, 64, 66,respectively, which may take the form of a coil. The IMD 16 may deliverdefibrillation shocks to the heart 12 via any combination of theelongated electrodes 62, 64, 66 and the housing electrode 58. Theelectrodes 58, 62, 64, 66 may also be used to deliver cardioversionpulses to the heart 12. Further, the electrodes 62, 64, 66 may befabricated from any suitable electrically conductive material, such as,but not limited to, platinum, platinum alloy, and/or other materialsknown to be usable in implantable defibrillation electrodes. Sinceelectrodes 62, 64, 66 are not generally configured to deliver pacingtherapy, any of electrodes 62, 64, 66 may be used to sense electricalactivity during pacing therapy (e.g., for use in determining activationtimes). In at least one embodiment, the LV elongated electrode 64 may beused to sense electrical activity of a patient's heart during thedelivery of pacing therapy. Electrodes used to sense a response fromcardiac tissue are transmitted to an A/D converter to convert the analogsignal to a digital signal. The digital signal is then transmitted tothe microprocessor 80. The microprocessor 80 determines the level ofresponse sensed at a particular electrode.

The configuration of the exemplary therapy system 10 illustrated inFIGS. 1-2 is merely one example. In other examples, the therapy systemmay include epicardial leads and/or patch electrodes instead of or inaddition to the transvenous leads 18, 20, 22 illustrated in FIG. 1.Further, in one or more embodiments, the IMD 16 need not be implantedwithin the patient 14. For example, the IMD 16 may deliverdefibrillation shocks and other therapies to the heart 12 viapercutaneous leads that extend through the skin of the patient 14 to avariety of positions within or outside of the heart 12. In one or moreembodiments, the system 10 may utilize wireless pacing (e.g., usingenergy transmission to the intracardiac pacing component(s) viaultrasound, inductive coupling, RF, etc.) and sensing cardiac activationusing electrodes on the can/housing and/or on subcutaneous leads.

In other examples of therapy systems that provide electrical stimulationtherapy to the heart 12, such therapy systems may include any suitablenumber of leads coupled to the IMD 16, and each of the leads may extendto any location within or proximate to the heart 12. Other examples oftherapy systems may include three transvenous leads located asillustrated in FIGS. 1-3. Still further, other therapy systems mayinclude a single lead that extends from the IMD 16 into the right atrium26 or the right ventricle 28, or two leads that extend into a respectiveone of the right atrium 26 and the right ventricle 28.

FIG. 4 is a functional block diagram of one exemplary configuration ofthe IMD 16. As shown, the IMD 16 may include a control module 81, atherapy delivery module 84 (e.g., which may include a stimulationgenerator), a sensing module 86, and a power source 90.

The control module 81 may include a processor 80, memory 82, and atelemetry module 88. The memory 82 may include computer-readableinstructions that, when executed, e.g., by the processor 80, cause theIMD 16 and/or the control module 81 to perform various functionsattributed to the IMD 16 and/or the control module 81 described herein.Further, the memory 82 may include any volatile, non-volatile, magnetic,optical, and/or electrical media, such as a random access memory (RAM),read-only memory (ROM), non-volatile RAM (NVRAM), electrically-erasableprogrammable ROM (EEPROM), flash memory, and/or any other digital media.

The processor 80 of the control module 81 may include any one or more ofa microprocessor, a controller, a digital signal processor (DSP), anapplication specific integrated circuit (ASIC), a field-programmablegate array (FPGA), and/or equivalent discrete or integrated logiccircuitry. In some examples, the processor 80 may include multiplecomponents, such as any combination of one or more microprocessors, oneor more controllers, one or more DSPs, one or more ASICs, and/or one ormore FPGAs, as well as other discrete or integrated logic circuitry. Thefunctions attributed to the processor 80 herein may be embodied assoftware, firmware, hardware, or any combination thereof.

The control module 81 may control the therapy delivery module 84 todeliver therapy (e.g., electrical stimulation therapy such as pacing) tothe heart 12 according to a selected one or more therapy programs, whichmay be stored in the memory 82. More specifically, the control module 81(e.g., the processor 80) may control the therapy delivery module 84 todeliver electrical stimulus such as, e.g., pacing pulses with theamplitudes, pulse widths, frequency, or electrode polarities specifiedby the selected one or more therapy programs (e.g., pacing therapyprograms, pacing recovery programs, capture management programs, etc.).As shown, the therapy delivery module 84 is electrically coupled toelectrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66, e.g., viaconductors of the respective lead 18, 20, 22, or, in the case of housingelectrode 58, via an electrical conductor disposed within housing 60 ofIMD 16. Therapy delivery module 84 may be configured to generate anddeliver electrical stimulation therapy such as pacing therapy to theheart 12 using one or more of the electrodes 40, 42, 44, 45, 46, 47, 48,50, 58, 62, 64, 66.

For example, therapy delivery module 84 may deliver pacing stimulus(e.g., pacing pulses) via ring electrodes 40, 44, 48 coupled to leads18, 20, and 22, respectively, and/or helical tip electrodes 42, 46, and50 of leads 18, 20, and 22, respectively. Further, for example, therapydelivery module 84 may deliver defibrillation shocks to heart 12 via atleast two of electrodes 58, 62, 64, 66. In some examples, therapydelivery module 84 may be configured to deliver pacing, cardioversion,or defibrillation stimulation in the form of electrical pulses. In otherexamples, therapy delivery module 84 may be configured deliver one ormore of these types of stimulation in the form of other signals, such assine waves, square waves, and/or other substantially continuous timesignals.

The IMD 16 may further include a switch module 85 and the control module81 (e.g., the processor 80) may use the switch module 85 to select,e.g., via a data/address bus, which of the available electrodes are usedto deliver therapy such as pacing pulses for pacing therapy, or which ofthe available electrodes are used for sensing. The switch module 85 mayinclude a switch array, switch matrix, multiplexer, or any other type ofswitching device suitable to selectively couple the sensing module 86and/or the therapy delivery module 84 to one or more selectedelectrodes. More specifically, the therapy delivery module 84 mayinclude a plurality of pacing output circuits. Each pacing outputcircuit of the plurality of pacing output circuits may be selectivelycoupled, e.g., using the switch module 85, to one or more of theelectrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 (e.g., a pairof electrodes for delivery of therapy to a pacing vector). In otherwords, each electrode can be selectively coupled to one of the pacingoutput circuits of the therapy delivery module using the switchingmodule 85.

The sensing module 86 is coupled (e.g., electrically coupled) to sensingapparatus, which may include, among additional sensing apparatus, theelectrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 to monitorelectrical activity of the heart 12, e.g., electrocardiogram(ECG)/electrogram (EGM) signals, etc. The ECG is a record of theelectrical activity of the heart as the impulse travels from the atriathrough the ventricles. The record is displayed in a waveform with threedistinct waves: P, QRS, and T. The ECG/EGM signals may be used tomonitor heart rate (HR), heart rate variability (HRV), heart rateturbulence (HRT), deceleration/acceleration capacity, decelerationsequence incidence, T-wave alternans (TWA), P-wave to P-wave intervals(also referred to as the P-P intervals or A-A intervals), R-wave toR-wave intervals (also referred to as the R-R intervals or V-Vintervals), P-wave to QRS complex intervals (also referred to as the P-Rintervals, A-V intervals, or P-Q intervals), QRS-complex morphology, STsegment (i.e., the segment that connects the QRS complex and theT-wave), T-wave changes, QT intervals, electrical vectors, etc.

The switch module 85 may also be used with the sensing module 86 toselect which of the available electrodes are used, e.g. to senseelectrical activity of the patient's heart. In some examples, thecontrol module 81 may select the electrodes that function as sensingelectrodes via the switch module within the sensing module 86, e.g., byproviding signals via a data/address bus. In some examples, the sensingmodule 86 may include one or more sensing channels, each of which mayinclude an amplifier.

In some examples, sensing module 86 includes a channel that includes anamplifier with a relatively wider pass band than the R-wave or P-waveamplifiers. Signals from the selected sensing electrodes that areselected for coupling to this wide-band amplifier may be provided to amultiplexer, and thereafter converted to multi-bit digital signals by ananalog-to-digital converter (ND) for storage in memory 82 as anelectrogram (EGM). In some examples, the storage of such EGMs in memory82 may be under the control of a direct memory access circuit. Thecontrol module 81 (e.g., using the processor 80) may employ digitalsignal analysis techniques to characterize the digitized signals storedin memory 82 to detect and classify the patient's heart rhythm from theelectrical signals. For example, the processor 80 may be configured tomeasure activation times of cardiac tissue using EGMs from one or moreelectrodes in contact, or in proximity, with cardiac tissue by employingany of the numerous signal processing methodologies known in the art.

If IMD 16 is configured to generate and deliver pacing pulses to theheart 12, the control module 81 may include a pacer timing and controlmodule, which may be embodied as hardware, firmware, software, or anycombination thereof. The pacer timing and control module may include oneor more dedicated hardware circuits, such as an ASIC, separate from theprocessor 80, such as a microprocessor, and/or a software moduleexecuted by a component of processor 80, which may be a microprocessoror ASIC. The pacer timing and control module may include programmablecounters which control the basic time intervals associated with DDD,VVI, DVI, VDD, AAI, DDI, DDDR, VVIR, DVIR, VDDR, AAIR, DDIR and othermodes of single and dual chamber pacing. In the aforementioned pacingmodes, “D” may indicate dual chamber, “V” may indicate a ventricle, “I”may indicate inhibited pacing (e.g., no pacing), and “A” may indicate anatrium. The first letter in the pacing mode may indicate the chamberthat is paced, the second letter may indicate the chamber in which anelectrical signal is sensed, and the third letter may indicate thechamber in which the response to sensing is provided.

Intervals defined by the pacer timing and control module within controlmodule 81 may include atrial and ventricular pacing escape intervals,refractory periods during which sensed P-waves and R-waves areineffective to restart timing of the escape intervals, and/or the pulsewidths of the pacing pulses. As another example, the pacer timing andcontrol module may define a blanking period, and provide signals fromsensing module 86 to blank one or more channels, e.g., amplifiers, for aperiod during and after delivery of electrical stimulation to the heart12. The durations of these intervals may be determined in response tostored data in memory 82. The pacer timing and control module of thecontrol module 81 may also determine the amplitude of the cardiac pacingpulses.

During pacing, escape interval counters within the pacer timing/controlmodule may be reset upon sensing of R-waves and P-waves. Therapydelivery module 84 (e.g., including a stimulation generator) may includeone or more pacing output circuits that are coupled, e.g., selectivelyby the switch module 85, to any combination of electrodes 40, 42, 44,45, 46, 47, 48, 50, 58, 62, or 66 appropriate for delivery of a bipolaror unipolar pacing pulse to one of the chambers of heart 12. The controlmodule 81 may reset the escape interval counters upon the generation ofpacing pulses by therapy delivery module 84, and thereby control thebasic timing of cardiac pacing functions, including anti-tachyarrhythmiapacing.

In some examples, the control module 81 may operate as an interruptdriven device, and may be responsive to interrupts from pacer timing andcontrol module, where the interrupts may correspond to the occurrencesof sensed P-waves and R-waves and the generation of cardiac pacingpulses. Any necessary mathematical calculations may be performed by theprocessor 80 and any updating of the values or intervals controlled bythe pacer timing and control module may take place following suchinterrupts. A portion of memory 82 may be configured as a plurality ofrecirculating buffers, capable of holding series of measured intervals,which may be analyzed by, e.g., the processor 80 in response to theoccurrence of a pace or sense interrupt to determine whether thepatient's heart 12 is presently exhibiting atrial or ventriculartachyarrhythmia.

The telemetry module 88 of the control module 81 may include anysuitable hardware, firmware, software, or any combination thereof forcommunicating with another device, such as the programmer 24 asdescribed herein with respect to FIG. 1. For example, under the controlof the processor 80, the telemetry module 88 may receive downlinktelemetry from and send uplink telemetry to the programmer 24 with theaid of an antenna, which may be internal and/or external. The processor80 may provide the data to be uplinked to the programmer 24 and thecontrol signals for the telemetry circuit within the telemetry module88, e.g., via an address/data bus. In some examples, the telemetrymodule 88 may provide received data to the processor 80 via amultiplexer. In at least one embodiment, the telemetry module 88 may beconfigured to transmit an alarm, or alert, if the pacing therapy becomesineffective or less effective.

The various components of the IMD 16 are further coupled to a powersource 90, which may include a rechargeable or non-rechargeable battery.A non-rechargeable battery may be selected to last for several years,while a rechargeable battery may be inductively charged from an externaldevice, e.g., on a daily or weekly basis.

After the LV lead 20 has been properly positioned on or near the LVtissue, schematically shown in FIG. 3, and the RV lead is in position, avariety of fusion pacing configurations (e.g. RV only pacingconfiguration, LV only pacing etc.) can be tested. Data generated fromeach pacing configuration can be useful in determining the optimal LVelectrode from which to pace the LV or the optimal RV electrode to pacethe RV. Each fusion pacing configuration employs a different LVelectrode (e.g. LV1, LV2, LV3, and LV4 etc.) or a different RV electrodefor pacing.

Exemplary methods and/or devices described herein evaluate theeffectiveness of cardiac resynchronization based on metrics ofelectrical dyssynchrony derived from the measured cardiac electricalactivation times for each fusion pacing configuration employing adifferent LV electrode. FIGS. 5-7 flow diagrams present differentexemplary methods for selecting an optimal LV electrode or RV electrode.

Exemplary method 100, depicted in FIG. 5, evaluates a fusion pacingconfiguration such as LV only pacing in order to determine which LVelectrode on lead 20 is optimal for pacing the LV. Each of the availablefusion pacing configurations, based on the selected LV only pacingelectrode, is serially tested and evaluated by programmer 24 as to itseffectiveness based on the metrics of electrical dyssynchrony. Theoptimal fusion pacing configuration is selected based on one or more ofthese metrics. While the methods are described relative to LV onlypacing, skilled artisans appreciate that the same principles can beapplied to RV only pacing. At block 102, the programmer 24 switches oneof the LV electrodes 44, 45, 46, 47 to a pacing mode while the other LVelectrodes remain in the sensing mode. The LV electrode that is selectedfor pacing the LV is designated as the j-th LV electrode. The first LVelectrode out of the plurality of LV electrodes to pace the LV isreferred to in the claims as the first LV electrode. The programmer 24includes a pulse generator that generates pacing pulses (e.g. 2-3 voltsamplitude) that are delivered through the pacing LV electrode to the LV.In one or more embodiments, the first LV electrode is paced at paced A-Vdelays (PAV) or SAV at least 60 ms shorter than the intrinsic delay.Intrinsic A-V delay is determined through the formula below:[Ventricular sensed event time (Vs)−Atrial-sensed event time(As)[Ventricular sensed event time (Vs)−Atrial-paced event time (Ap)].

The IMD is configured to determine the timing and interval between theseevents. The electrogram signals at each of the non-pacing LV electrodesas well as the RV electrode are transmitted to an ND converter thatconverts the analog signals to digital signals. Digital signals are thentransmitted to the microprocessor 80 so that signals can be measured andthen stored into memory 82 at operation 104.

At block 106, after obtaining the electrical activation times (e.g.determined with respect to the timing of the earliest ventricular pacingor any other suitable means) at non-pacing electrodes, themicroprocessor 80 determines the weighted electrical dyssynchrony indexfor the first fusion pacing configuration. Electrical dyssynchony orcardiac dyssynchrony involves improperly timed electrical activation ofone or more different parts of the heart.

The fusion index of LV electrical dyssynchrony [FI (j, A)] can becomputed for each pacing electrode j from a linear combination ofelectrical activation times (LVAT(i, A)) at each non-pacing LV electrodedenoted by i and RV electrical activation times RVAT(i, A) at each RVelectrode i. “A” of FI (j, A) refers to the atrio-ventricular delaybetween atrial sense (or pace) and the ventricular pacing pulse. Adetermination of FI for each LV electrode may be made initially at anominal value of A such as 50 ms.

FI is determined by a weighted linear combination of electricalactivation times in which individual weights are determined dependingupon the lead-geometry and the inter-electrode spacing on the lead. Inparticular, FI is weighted by a suitable factor w(i, j) that is based onthe distance of the non-pacing electrode (designated “i”) from thepacing electrode (designated “j”). Accordingly, the equation forcalculating a weighted FI is as follows:FI(j,A)=Σ_(i=1) ^(n) w _(LV)(i,j)|LVAT(i,A|)+Σ_(i=1) ^(m) w_(RV)(i,j)|RVAT(i,A|)where “n” is the total number of LV electrodes and m is the total numberof RV electrodes.

Only valid FI are used to determine an optimal LV electrode from whichto pace. Before the electrode evaluations are performed, the leftventricular capture management routine may be evoked to determine theminimum thresholds required for left ventricular capture for each LVpacing vector. The evaluations of FI are performed while pacing the LVat outputs with adequate margins (≧1 V) above the minimum thresholddetermined by the left ventricular capture management routine for eachLV pacing vector.

Additionally, automatic LV capture detection is turned on to ensure thatthe pacing pulse delivered captures each ventricle. FI is not computedfor instances where the pacing pulse does not capture the LV. Capturedetection can be verified by determining the amplitude of an evokedresponse at the pacing electrode within a short duration of time afterdelivery of the pace. More particularly, capture detection can beverified by observing an initial negative deflection within 20-60 msafter the pace delivery, on the EGM viewed between the pacing electrodeand an indifferent electrode like the device case or an RV coilelectrode. Exemplary capture can be indicated by an amplitude greaterthan 0.5 mV.

The FI may be calculated over multiple (N) beats, where N can be anynumber between 5 to 10, during pacing from a selected LV electrode toensure that measurements are consistent and repeatable. A coefficient ofvariation which is provided by the standard deviation of FI divided bymean FI index over N number of beats multiplied by 100 (to express as apercentage) may be computed to measure the amount of variability in FIfor a given LV pacing vector. If the coefficient of variation is lessthan a certain percentage threshold (which can be any number from 5% to20%), the FI measurements are considered to be valid and the mean or themedian of the FI values may be taken as the representative measure of FIfor that particular LV pacing electrode.

FI is typically computed with the atrioventricular delay (A) set at aconstant value when evaluating each LV electrode. For example, the A-Vdelay can be set at a preselected value (e.g. 50 to about 140 ms etc.)for each fusion pacing configuration where the pacing cathode is LV1,LV2, . . . LVn. In another embodiment, the pre-selected AV delay (A) maybe determined from the intrinsic AV delay (iAV) by the following scheme:

-   -   if iAV−60 ms≧80 ms,        -   A=iAV−60 ms    -   else        -   A=80 ms

Assume A=50 ms while evaluating each of the LV electrodes as isdiscussed in greater detail below. Additionally, skilled artisansappreciate that the activation time for the pacing electrode whichcaptures the tissue may be 0 or may be skipped.

After the FI has been determined for the first LV electrode, theprogrammer 24 automatically selects a second fusion pacing configurationin which a second LV electrode paces the LV at operation 108. Theprogrammer 24 causes the pulse generator to generate pacing pulses (e.g.2-3 volts amplitude) through the second LV electrode to the LV. Thenon-pacing LV electrodes record the electrical response (e.g.electrograms.) from the LV tissue. The electrogram signals aretransmitted to an A/D converter that converts the analog signals todigital signals. Digital signals are then transmitted to themicroprocessor 80 so that electrogram signals can be measured,activation times can be computed and then stored into memory 82 atoperation 110. After obtaining the electrical activation times atnon-pacing electrodes, the microprocessor 80 determines a weightedfusion index associated with the second LV pacing electrode at operation112. Skilled artisans appreciate that blocks 108-112 are repeated forall of the remaining LV electrodes (e.g. LV3, LV4 etc.) at the distalend of lead 20.

Once two or more valid FI have been calculated, electrode eliminationrules can be applied to the FI to eliminate LV electrodes in order todetermine the optimal LV electrode at operation 114. The FI for eachelectrode can be determined for the set of electrodes before applicationof the set of rules. Alternatively, the rules can be applied afterdetermining a FI for any two electrodes and once one of the twoelectrodes is eliminated, a FI is calculated for yet another electrodeto be compared to the FI of the remaining electrode.

Examples of the manner in which FI are calculated are presented below asto the set of LV electrodes (i.e. left ventricle electrode 1 (LV1) 44,left ventricle electrode 2 (LV2) 45, left ventricle electrode 3 (LV3)46, and left ventricle 4 (LV4) 47 etc.) shown on the LV medicalelectrical lead 20 and a RV bipolar lead; however, it is appreciatedthat teachings presented herein can be applied to two or more LVelectrodes on a medical electrical lead.

While pacing from LV1 during fusion pacing and A=50 ms, the FI iscomputed below. For this nominal value of A, the FI for the fusionpacing with the j-th LV electrode and the activation time at the i-th LVelectrode during such fusion pacing are represented by FI (j) and AT(i)respectively. The weighted FI for pacing at LV1 can be rewritten asfollows:FI(1)=|LVAT(1)|+|LVAT(2,3)|+|LVAT(4)/2|+|RVAT(1)|

where LVAT(2,3)=[LVAT(2)+LVAT(3)]/2

Since LV2 and LV3 are substantially close, the AT of LV2 and LV3 areaveraged together. The AT associated with LV4 is multiplied by aconstant number w(i, j). W(i, j) is a weighting factor that depends onthe distance from LV1 to LV4 as compared to the distance between LVelectrodes (2,3) and LV1. Skilled artisans will appreciate that althoughthe RV bipolar lead consists of two electrodes (e.g. RV tip and RVring), only RVAT (1) is represented in the equation since the RVelectrodes are closely spaced to one another. Closely spaced electrodesmeasure about the same activation time. However, if the RV electrodeswere not closely spaced, the equation could be modified to include thesecond RV electrode. In one or more embodiments, since only LVelectrodes are selected, a uniform weighting factor (e.g. “1) can beassigned to each RV electrode(s).

In this example, w(4,1) is ½ since the distance from LV1 to LV4 is twiceas long as the distance from electrodes (2,3) to LV1. W(i, j) can beadjusted depending upon the LV medical electrical lead and the spacingused between the plurality of electrodes thereon.

Evaluation of FI and activation propagation is also performed whilepacing from other LV electrodes 2, 3 and 4 in the quadripolar lead 20during fusion pacing. The equation for calculating weighted FI at LV2 orLV3 is as follows:FI(2)=|LVAT(1)|+|LVAT(2,3)|+|LVAT(4)|+|RVAT(1)|FI(3)=|LVAT(1)|+|LVAT(2,3)|+|LVAT(4)|+|RVAT(1)|where LVAT(2,3)=[LVAT(2)+LVAT(3)]/2Since the spacing between LV2 and LV3 is less than 2 mm, and LV1 and LV4are about equidistant from LV2 and LV3, the activation times areweighted equally while computing FI for LV2 and LV3.The equation for calculating a weighted FI at LV4 is as follows:FI(4)=|LVAT(1)/2|+|LVAT(2,3)|+|LVAT(4)|+|RVAT(1)|where LVAT(2,3)=[LVAT(2)+LVAT(3)]/2After weighted FI calculations are performed, the optimal LV electrodeis selected at block 114.

FIGS. 6A-6B provide exemplary methods in which an optimal electrode isselected from a set of electrodes to perform fusion pacing. FIG. 6A, forexample, shows a method 200 in which a process of electrode eliminationis used to determine the optimal LV electrode from the plurality LVelectrodes (e.g. LV1, LV2, LV3, and LV4). The process of eliminationemploys two different types of electrode comparisons that are used toeliminate an electrode from each pair of electrodes until the soleremaining electrode is deemed to be the optimal LV electrode. Theprocess of eliminating an electrode begins at block 202 in whichactivation times are measured at the LV electrodes (e.g. LV1, LV2, LV3,and LV4) during baseline rhythm which may constitute RV only pacing orintrinsic rhythm. RV only pacing occurs when the pulse generator fromthe programmer 24 delivers electrical stimulation (i.e. pacing pulses)through an RV electrode to the RV and none of the LV electrodes are usedto pace the LV. Sensing the activation times at all of the LV electrodes(e.g. LV1, LV2, LV3, and LV4) during RV only pacing or during intrinsicrhythm can be performed any time after LV lead 20 has been placed nearand/or on LV tissue.

At block 204, the activation times associated with each of the LVelectrodes are stored into the memory 82. At block 206, variablesthreshold (T) level, integer (I), and total number of electrodes (N)(e.g. N=4 on the distal end of lead 20) are initialized, set, and storedinto memory 82. Threshold T can be predetermined and input into theprogrammer 24 by the user before evaluating each LV electrode (e.g. LV1,LV2, LV3, LV4). Preferably, T equals 15 ms or less. A value of T equalto 15 ms or less can be typical of a left bundle branch block (LBBB)patient with a QRS of 150 ms. Additionally, T equal to 15 ms or less istypically about a 10% time of total ventricular activation. In one ormore other embodiments, T equals 10 ms or less.

I and N are used in a counting loop (i.e. blocks 206, 230 and 232) thatensures that data for each LV electrode (e.g. LV1, LV2, LV3, and LV4)are analyzed before the optimal LV electrode is selected. I=1 since FIis determined for only one LV electrode at block 208 by processor 80 andstored in memory 82. The data for determining the FI for one LVelectrode can be selected from any one of the LV electrodes (e.g. LV1,LV2, LV3, and LV4). At block 210, data for another LV electrode isretrieved from memory 82 by processor 80. Determining the FI for anotherLV electrode means any other LV electrode data not previously analyzed.For example, if the FI for one LV electrode at block 208 is data relatedto LV1, then data for another LV electrode can be related to LV2, LV3,or LV4. For the sake of illustration, assume that the data for anotherLV electrode is associated with LV2. Therefore, the FI for LV2 iscalculated by processor 80 and stored in memory 82.

At block 212, the difference in magnitude between one FI data andanother FI data is determined. For example, the FI data for oneelectrode (i.e. LV2) is subtracted from FI data for another electrode(i.e. LV1). At block 214, the difference between one FI data (i.e. FI 1)and another FI data (i.e. FI 2) is compared to a threshold level T (alsoreferred to as delta T or ΔT). At block 216, if the difference is notless than T, then the NO path can be followed to block 218. At operation218, whichever electrode is associated with a larger FI is automaticallyeliminated from consideration as a potential optimal LV electrodeirrespective of the eliminated electrode's activation time obtainedduring intrinsic rhythm or RV only pacing.

The counting loop increases the variable I by one at block 230. At block232, a determination is made as to whether I=N. Since after the firstpass of the counting loop I=2 and N=4, the NO path transfers control toblock 210 to retrieve FI data for yet another LV electrode. FI is thencalculated for yet another LV electrode (e.g. LV3) and then stored intomemory 82. Skilled artisans appreciate that after an electrode iseliminated, at either block 218 or 228, and FI data for anotherelectrode is retrieved, a swapping operation may be performed. Forexample, if data for LV2 is initially designated as “another LVelectrode” and LV2 is eliminated, then data for LV3 is swapped for theFI data for LV2 and the FI data for LV3 is now stored in the registerfor “another FI data” at block 210. The electrode pair comparisons arethen between LV1 and LV3 and so on.

Returning to block 216, if the difference in FI value is less than T,the YES path transfers control to block 222. At block 222, the baseline(intrinsic rhythm or RV only pacing) AT data for one electrode (i.e.LV1) is compared to the baseline AT data for another electrode (i.e.LV3). The baseline AT data is preferably obtained during intrinsicrhythm or RV only pacing. Comparing one baseline AT to another baselineAT can involve a sorting function that places the data in ascendingorder or descending order. At block 224, a determination is made as towhether one baseline AT is less than another baseline AT. If onebaseline AT is less than another baseline AT, the YES path can befollowed to block 226.

Returning to block 223, if one baseline AT is equal to the otherbaseline AT, then both electrodes are retained in a preference list. Atblock 225, one of the two electrodes can be eliminated based uponadditional or other criteria such as lower capture threshold, higherimpedance (i.e., reduced energy required to pace), or absence of phrenicstimulation could be considered (by the user) to select the bestelectrode of two electrodes that have equivalent ATs.

At block 226, one electrode (i.e. LV1) is eliminated. I is incrementedby 1 at block 230. At block 232, a determination is made as to whetherI=N, which essentially determines whether FI data has yet to beretrieved.

Returning to block 224, if one baseline AT is not less than anotherbaseline AT, the NO path can be followed to block 228 in which anotherelectrode (i.e. LV2) is eliminated. The counting loop at block 232 isthen used to determine whether any additional FI data must be processed.At block 232, once I=N, no additional FI data needs to be processed.Therefore, the YES path can be followed to block 234. The optimalelectrode is then designated as the LV electrode that remains or has notbeen eliminated. The optimal LV electrode is set to pace the LVautomatically by programmer 24 or manually by the user.

Examples, presented below, show the electrode elimination process usedto select an optimal LV electrode. In these examples, assumptions aremade. For blocks 222, and 224, activation times for the LV electrodesare performed during RV only pacing or during intrinsic rhythm. Incontrast, the FI data was generated using the fusion pacingconfigurations, as previously described herein. Additionally, aquadripolar LV lead 20 is used that includes four LV electrodes, LV1,LV2, LV3, and LV4; however, skilled artisans appreciate that otherembodiments could use two or more LV electrodes on a lead 20 such as twoor more electrodes on one lead and two or more electrodes on anotherlead. Each example will be described relative to FIG. 6A.

In the first example, assume that the order of activation times duringRV only pacing or intrinsic rhythm is AT(LV4)>AT(LV1)>AT(LV2)>AT(LV3)with LV4 being the latest activation time and LV3 being the earliestactivation time. Assume also that the values of FI, determined from thefusion configurations previously discussed are as follows: FI(1)=50 ms,FI(2)=55 ms, FI(3)=58 ms, and FI(4)=74 ms. Other assumptions include Ais a constant (e.g., 50 ms) and a predetermined threshold T of 15 ms isused to analyze the FI data. Processor 80 retrieves FI data such asFI(1) and FI(2) at blocks 208, 210, respectively.

At block 212, the difference in magnitude between FI(1) and FI(2) iscalculated as follows:FI(2)−FI(1)=55 ms−50 ms=5 ms

At block 214, the difference in FI(1) and FI(2) is compared to thethreshold T. At block 216, a determination is made as to whether thedifference in FI(1) and FI(2) is less than the predetermined thresholdof 15 ms. Since the difference (i.e. 5 ms) in FI(1) and FI(2) is lessthan T, the YES path is followed to block 222 in which the AT values(i.e. AT(1), AT(2)) are compared. In one or more embodiments, thecompare function can also include sorting the activation times inascending order or descending order.

At block 223, if one baseline AT is equal to the other baseline AT, thenboth electrodes are retained in a preference list. One of the twoelectrodes is eliminated based upon the previously described criteria atblock 225. If one AT does not equal another AT, the NO path goes toblock 224.

At block 224, a determination is made as to whether one AT (i.e. AT1) isless than another AT (i.e. AT2). As is known from the given facts, theactivation time for one AT (i.e. AT1) is greater than another AT (i.e.AT2). The NO path can be followed to block 228, which causes theelimination of another electrode (i.e. LV2). The variable I is increasedby 1 at block 230. At block 232, a determination is made as to whetherI=N. Since I=2 and N=4, I does not equal N. The NO path returns to block210 for processor 80 to retrieve from memory 82 another FI value foranother LV electrode (e.g. LV3).

The FI value of LV3 is then subtracted from the FI value for LV1 atblock 212, as shown below.FI(3)−FI(1)=58 ms−50 ms=8 ms

The difference in magnitude (i.e. 8 ms) between FI(1) and FI(3) is lessthan the predetermined threshold of 15 ms at block 216. The YES path canbe followed to block 222. At block 222, the activation times betweenAT(1) and AT(3) are compared to each other. As previously stated, AT(1)is greater than AT(3). LV3 is then eliminated based on its earlieractivation time compared to LV1 at block 228.

At block 230, the variable I is again increased by 1 which causes I=3. Adetermination is made as to whether I=N at block 232. Since I does notequal N, the NO path is followed to block 210. The FI data for the nextelectrode, FI(4), is then then retrieved at block 210.

FI(1) data, associated with LV1, is subtracted from FI(4) at block 212.At block 214, the difference in FI values is 24 ms, which is greaterthan the pre-determined threshold of 15 ms. The NO path can be followedto block 218 in which the electrode to be eliminated is associated withthe larger FI data. The electrode with the larger FI, i.e. LV4, iseliminated without any comparison being performed between the activationtimes of LV1 and LV4.

At block 230, I is again incremented by 1 causing I=4. At block 232, adetermination is made as to whether I=N. Since I=4 and N=4, then I=N.The YES path can be followed to block 234, which designates the optimalelectrode is LV1 since LV1 is the last remaining electrode that was noteliminated in the exhaustive electrode-pair comparisons. LV1 is thenselected as the final electrode for delivering CRT.

A second example shows how the selection is made when FI values of allelectrodes are almost equivalent or similar. For example, assume theorder of activation times during intrinsic rhythm (or RV only pacing)are such that AT(LV4)>AT(LV1)>AT(LV2)>AT(LV3). LV4 is associated withthe latest activation time and LV3 is associated with the earliestactivation time. From the fusion pacing configurations, the FI valueswere determined such that FI(1)=30 ms, FI(2)=33 ms, FI(3)=25 ms, andFI(4)=28 ms. Referring to FIG. 6A-B, FI data is retrieved for one LVelectrode such as FI(1) at block 208. At block 210, FI data is retrievedfor another LV electrode such as FI(2) at block 212. At block 212, thedifference in FI values is calculated follows:FI(2)−FI(1)=33 ms−30 ms=3 ms

At block 214, the difference in FI(1) and FI(2) is compared topredetermined threshold of 15 ms. As shown above, the difference inFI(1) and FI(2) is only 3 ms which is less than the predeterminedthreshold of 15 ms. At block 216, a determination is made as to whetherthe difference in FI values is less than the threshold. Since thedifference is 3 ms is less than 15 ms, the YES path can be followed toblock 222 in which one AT (i.e. AT(1)) is compared to another AT (i.e.AT(2)). From the comparison, it was determined that AT(1) is greaterthan AT(2). At block 224, a NO path can be followed to block 228 thateliminates another electrode (i.e. LV2). At block 230, I is incrementedby I causing I=2. At block 232, a determination is made as to whetherI=N. Since I=2 and N=4, I does not equal N. Therefore, the NO pathreturns to block 210 in which another FI data (i.e. FI3) is retrievedfrom memory 82.

At block 212, the difference between FI(1) and FI(3) is calculated asfollows:FI(1)−FI(3)=30 ms−25 ms=5 ms

The difference in FI values of LV1 and LV3 is 5 ms which is less thanthe threshold value of 15 ms at block 216. The YES path can be followedto block 222 which compares AT(1) to AT(3). Since AT(3) is greater thanAT(1), the electrode LV3 is eliminated at block 228 based on its earlieractivation time compared to the electrode LV1. Again, I is incrementedby 1 at block 230 and another determination is made as to whether I=N atblock 232. Since I=3, I does not equal N. Therefore, another FI datasuch as FI(4) is retrieved from memory 82.

LV4 can then be compared with the electrode LV1. The difference in FIvalues of electrode LV1 and the electrode LV4 is 2 ms. At block 224, oneAT is found to be less than another AT. The electrode LV1 is eliminateddue to AT(LV1) having an earlier activation time compared to AT(4).Again, I is incremented by 1 causing I=4. Since I=N at block 232, theoptimal electrode is LV4. LV4 is chosen as the final or optimalelectrode from which to pace the LV since LV4 was not eliminated.

A third example is presented in which activation times during RV onlypacing or intrinsic rhythm of the four electrodes are such thatAT(LV4)>AT(LV1)>AT(LV2)>AT(LV3). Additionally, the FI values generatedfrom the fusion pacing configurations are FI(1)=60 ms, FI(2)=40 ms,FI(3)=38 ms, and FI(4)=62 ms. Referring to FIG. 6, processor 80retrieves FI(1) data and FI(2) data from memory 82 at blocks 208, 210,respectively. At block 212, the difference in FI values can becalculated by the following:FI(1)−FI(2)=60 ms−40 ms=20 ms

At block 216, since the difference in FI values associated with LV1 andLV2 is 20 ms which exceeds the threshold of 15 ms, the NO path can befollowed to block 218 in which the electrode with the higher FI value,i.e. electrode LV1 is eliminated. I is incremented by 1 at block 230. Adetermination is then made as to whether I=N at block 232. Since I=2,and N equals 4, the NO path returns to block 210 to retrieve FI(3) data.

At block 212, the difference in FI values can be calculated as follows:FI(3)−FI(2)=38 ms−40 ms=−−2 ms

Since the difference in magnitude between FI(2) and FI(3) is 2 ms, whichis less than the threshold of 15 ms, the YES path can be followed toblock 222. At block 222, one AT (i.e. LV3) is compared to another AT(i.e. LV2). LV3 is associated with a AT that is less than the AT forLV2. At block 224, a determination is made as to whether one AT (i.e.LV3) is less than another AT (i.e. LV2). At block 226, electrode LV3 iseliminated.

Again, I is incremented by 1 at block 230. Therefore, I=3. At block 232,I does not equal N since I=3 and N=4; therefore, at block 210, FI(4) isretrieved from memory 82.

At block 212, the difference between FI(4) and FI(2) can be shown asfollows:FI(4)−FI(2)=62 ms−40 ms=22 ms

Since the difference in their FI values is 22 ms, well above thethreshold of 15 ms, the NO path can be followed to block 218. At block218, the electrode associated with the larger FI value is eliminated.Since FI(4) is larger (i.e. 62 ms) than FI(2) (i.e. 40 ms), LV4 iseliminated. I is again incremented by 1 at block 230 thereby causing Ito be equal to 4. At block 232, I=N; therefore, the YES path can befollowed to block 234. The optimal electrode is LV2. LV2 is then used topace the LV.

The method embodied in FIG. 6B is the same as FIG. 6A except block 225is replaced by block 227. As previously described relative to block 223,if one baseline AT is equal to the other baseline AT, then bothelectrodes are retained in a preference list. One of the two electrodescan be eliminated based upon additional or other criteria. For example,the pacing pulse can be automatically adjusted (e.g. increased ordecreased) at block 227. Equivalent electrodes are re-evaluated undermethod 200 by returning to block 202 using the new pacing criteria todetermine whether a difference exists between the two electrodes. Forexample, the pacing pulse can be increased by 0.25 volts, 0.5 volts,0.75 volts and so on. After rechecking the electrodes under method 200using the increased pacing pulse, more than likely, a difference willexist between the two electrodes and the electrode that under performsis eliminated. If not, the pacing criteria can again be modified and theelectrodes rechecked under method 200. The pacing criteria can becontinuously adjusted and the electrodes evaluated under method 200until a difference exists between the electrodes and one of theelectrodes can be eliminated. If one AT does not equal another AT, theNO path goes to block 224.

A set of LV electrode elimination rules can be summarized below whichcan be applied to scenarios in which an anatomic block is present or notpresent. An anatomic block is a difference between two AT that isgreater than a threshold T_(AT). One LV electrode elimination rule isthat when all electrodes have equivalent FI values, the LV electrodewith the latest activation during RV only pacing or intrinsic rhythm isselected for final CRT therapy. However, if one LV electrode isassociated with a significantly higher FI compared to another LVelectrode (i.e. a difference exceeding the predetermined threshold), theelectrode with the higher FI is eliminated as a possible choice,irrespective of the activation times during intrinsic rhythm or RV onlypacing.

In one or more embodiments, once an optimal LV electrode is chosen, anoptimal delay such as A-V delay (A) can be determined through exemplarymethod 300 presented in flow diagram of FIG. 7, respectively. In one ormore embodiments, A-V delay optimization occurs in a similar manner asthat which was performed to select the optimal LV electrode from whichto pace. In one or more embodiments, A-V delay optimization can beperformed through a use of a weighted sum of activation times forvarious A-V delays. The A-V delay that results in the lowest electricaldyssynchrony is selected and programmed into the programmer 24.

In order to determine the optimal A-V delay for fusion pacing such as LVonly fusion pacing, a FI must be calculated for at least two or more A-Vdelays. FI(j, A) represents the electrical dyssynchrony during fusionpacing LV electrode j. “A” represents an A-V delay and LVAT(i, A) andRVAT(i, A) represents activation time at LV electrode i during fusionpacing and activation time at RV electrode i respectively.

The FI equation is as follows:FI(j,A)=Σ_(i=1) ^(n) w _(LV)(i,j)|LVAT(i,A|)+Σ_(i=1) ^(m) w_(RV)(i,j)|RVAT(i,A|)where “n” is the total number of LV electrodes and m is the total numberof RV electrodes used in computation of the fusion index. For a standardCRT implantable device involving a single bipolar RV lead and aquadripolar LV lead, fusion indices during pacing from each of the LVelectrodes may be computed as follows for a given A-V delay A:FI(1,A)=|[LVAT(2,A)+LVAT(3,A)]/2|+|LVAT(4,A)/2|+|RVAT(1,A)|FI(2 or 3,A)=|LVAT(1,A)|+|LVAT(3 or 2,A)|+|LVAT(4,A)|+|RVAT(1,A)|FI(4,A)=|LVAT(1,A)/2|+|[LVAT(2,A)+LVAT(3,A)]/2|+|RVAT(1,A)|Skilled artisans will appreciate that although the RV bipolar leadconsists of two electrodes (e.g. RV tip and RV ring), only RVAT (1,A) isrepresented in the equation since the RV electrodes are closely spacedto one another. Closely spaced electrodes measure about the sameactivation time. However, if the RV electrodes were not closely spaced,the equation could be modified to include the second RV electrode.

To better understand the relationship between LVAT and RVAT and howthese times are calculated, it may be useful to examine a ventricularelectrogram, which shows changes in electrical potential at thecorresponding LV and RV electrodes (e.g. LV electrode-can, LVelectrode-RV coil, RV electrode-can, RV tip-RV ring etc.). FIG. 8, forexample, shows an atrial event is sensed by the right atrial electrodes.The atrial event may be used as a timing marker or timing reference. Thewindow, used to compute activation times for the depolarization signals,can be defined as extending from the atrial event and ending afterexpiration of a certain time period (e.g. 400 ms window timed from theatrial event). All computed activation times could be measured from thetiming of the atrial event.

Referring to FIG. 8, after the atrial event is sensed by one of theelectrodes a ventricular pacing stimulus is then delivered through LV1to the left ventricle at an atrioventricular delay (A) while no pacingstimulus is delivered to the RV. The upper panel of FIG. 8 shows a RVfar-field electrogram (RV ring-Can). The lower panel of FIG. 8 shows afar-field LV electrogram which is the electrical activity measuredrelative to the electrode that is the greatest distance away from thepacing electrode (i.e. measured from LV4—RV coil electrodes).Computation of activation times from far-field electrograms involvesdetermining the time corresponding to the steepest negative slope of theelectrogram during the depolarization cycle. These times for the RV andLV far-field electrograms are indicated by t-RV and t-LV on the upperand lower panels respectively. Once the appropriate timing on thewaveform is determined, all activation times may be referenced to thetiming of the delivery of the ventricular pace. Consequently, theright-ventricular activation time is RVAT(1,A)=tRV−A and LV activationtime at electrode 4 is LVAT(1,A)=tLV4−A where tRV and tLV4 are the timescorresponding to the most negative slope with respect to each signalwithin the defined window (i.e. 400 ms window). As shown in FIG. 8, tRVand tLV4 extend from the beginning of the atrial event to timecorresponding to the timing steepest slope of the corresponding farfieldelectrograms. The window, as previously described, starts with an atrialsensed event or an atrial paced event.

Though this specific example describes determination of activation timesfrom far-field electrograms, the same can be done from near-fieldelectrograms. For near-field electrograms (e.g. RV tip—RV ring),computation of activation time involves determining the timing of themaximum peak or the minimum valley. In case of a biphasic near-fieldwaveform, the point of zero-crossing may be also taken as thecorresponding activation time. As in the example, activation times ondifferent electrodes may then be referenced with a common timingfiducial or marker, like the timing of the atrial event).

As previously stated, only valid FI are used to determine an optimal LVelectrode from which to pace. Data is omitted when the pacing stimulusdelivered to LV fails to capture because of insufficient energy. In analternative embodiment, LV pacing is delivered at maximum energy toprevent the scenario of failure to capture because of insufficientenergy. The programmer 24 can automatically choose A-V delays rangingfrom a lowest value of 40 ms to a highest value of 260 ms, in incrementsof 5, 10, 15 or 20 ms for atrial sensing. The same values are alsoselected during atrial pacing.

After selecting the A-V delays, the programmer 24 causes the pulsegenerator to generate pacing pulses (e.g. ranging from about 0.25 voltsto about 8 volts and more preferably, between 2-3 volts) that aredelivered through the optimal LV electrode to the LV. The physiologicalresponse to the pacing pulses can be observed.

After measuring the electrical activation times at non-pacing electrodesat operation 304, the microprocessor 80 determines fusion index for thefirst A-V delay using the FI equation above associated with the optimalLV pacing electrode at operation 306. For example, the weighted sumequation could take into account the physical spacing, as previouslydiscussed, between the LV electrodes on the LV lead 20. For example, theelectrical dyssynchrony metric for fusion pacing from LV1 electrode at aA-V delay of 40 ms can be expressed as follows:FI(1,40)=AT(1,40)+AT([2,3],40)+AT(4,40)/2 whereinAT([2,3],40)=[AT(2,40)+AT(3,40)]/2

Since LV2 and LV3 are substantially close, the AT of LV2 and LV3 areaveraged together. The AT associated with LV4 is multiplied by aconstant number W. W is the distance from LV1 to LV4 as compared to thedistance from LV electrodes (2,3) to 1. In this example, W is ½ sincethe distance from LV1 to LV4 is twice as long as distance from electrode(2,3) to LV1. W can be adjusted depending upon the LV medical electricallead and the spacing used between the plurality of electrodes thereon.

The FI equation that is used to calculate the weighted fusion index fora given value A-V delay depends on the optimal LV electrode that isselected. For example, if LV1 is the optimal LV electrode, then FI(1) isused to calculate the FI for each of the A-V delays that are beingtested. If LV2 is the optimal LV electrode then FI(2) is used tocalculate and optimize the A-V delay. If LV3 is the optimal LV electrodethen FI(3) is used to calculate and optimize the A-V delay. If LV4 isthe optimal LV electrode then FI(4) is used to calculate and optimizethe A-V delay.

After a FI has been determined for the first A-V delay, the programmer24 automatically selects a second A-V delay. Again, pacing pulses aredelivered through the LV electrode at a second A-V delay while thesensing LV electrodes sense at operation 308. The activation times forthe non-pacing LV electrodes are then measured for the second A-V delayat operation 310. The FI for the second A-V delay is calculated atoperation 312 using the same FI equation that was used to calculate theFI for the first A-V delay. After determining the second FI for a secondA-V, the programmer 24 automatically selects a third A-V delay and thenthe programmer 24 sends pacing pulses to the RV electrode or the LVelectrode. A third FI is then calculated for the third A-V delay. Afterthe third FI is calculated, the programmer 24 automatically calculatesup to N number of A-V delays. Typically, the programmer 24 automaticallytests N (e.g. N can be 12-20 etc.) number of sensed A-V delays and Mnumber of paced A-V delays for a resting cycle-length (e.g. time (ms)between two events such as successive atrial events). Typically N equalsM, although skilled artisans will understand that N does not have to beequal to M since determining FI values for sensed A-V delays is adifferent operation than paced A-V delays. Generally, the programmer 24tests less than 100 A-V delays. In one or more other embodiments,programmer 24 can automatically test 20 or less A-V delays. In yetanother embodiment, programmer 24 can automatically test 10 or less A-Vdelays. Negative A-V delays are not tested because pre-excitation ofventricles before the atrial activation is not hemodynamically optimal.

Table 1, presented below, provides an example of FI results for SA-Vdelays that ranges from a short delay (i.e. 40 ms) to a long delay (i.e.260 ms). Each A-V delay is automatically separated by predetermined timeincrements (i.e. 20 ms) although other suitable time incremental values(e.g. 5 ms, 10 ms, 15 ms etc.) can also be used. Fusion pacing from LVor RV electrodes performed using a particular A-V delay, whilemaintaining the V-V delay at a constant or fixed nominal value allowsexemplary data to be generated for Table 1. The A-V delay that providesa minimum FI is selected as an optimal A-V delay. In this example, theoptimal A-V delay is 120 ms that corresponds to a minimum FI.

TABLE 1 FI for a range of sensed A-V (SA-V) delays at resting heart rateSA-V delay (ms) 40 60 80 100 120 140 160 180 200 220 240 260 FI(ms) 3939 32 28 25 29 36 41 45 46 46 46In a situation in which two or more A-V delays have the same minimum FI,the lowest A-V delay is selected as the optimal A-V delay.

To evaluate an optimal A-V delay changes during atrial pacing, atrialpacing is initiated at a rate equal to or just above the patient'sresting sinus rate. Table 2 summarizes fusion indices (FI) atdifferently paced A-V delays (PAV) that have been computed using asimilar method as that which is described relative to SAV. The optimalPAV in this case is 160 ms. Since both PAVs of 160 and 180 ms have thesame fusion index, the lesser of the two PAVs is selected.

The ΔAV_(rest) is the difference between optimal PAV and optimal SAV andis noted as follows:ΔAV_(rest)=optimal PAV−optimal SAV=(160−120)ms=40 ms.

Atrial pacing can also be initiated at decreasing cycle-lengths in stepsof 50 ms from the resting cycle-length. The same procedure can berepeated in order to identify the optimal PAV at each cycle-length. Forexample, the lowest FI is identified and then the corresponding PA-V isselected. The corresponding optimal SAV for each cycle-length may be setby subtracting ΔAV_(rest) from the optimal PAV at that cycle-length. Therange of cycle-lengths covered in this manner may start from the restingcycle-length and end in the upper atrial tracking rate.

TABLE 2 FI for a range of PAV delays at atrial pacing with cycle- lengthequal or just above the resting heart rate PA-V delay (ms) 40 60 80 100120 140 160 180 200 220 240 260 FI (ms) 39 39 39 32 30 28 25 25 28 34 4046

Table 3 is a look-up table of optimal PAV and SAV values for differentcycle-lengths that can be used for optimal and dynamic adaptation of A-Vdelay corresponding to different sensed or paced cycle-lengths. Inparticular, A-V optimization can automatically adjust A-V delaysaccording to changes in heart rates (e.g. faster heart rates or shortercycle-lengths). The programmer 24 or IMD 16 can adjust the AV delay byusing the look-up table that relates cycle length, PAV and/or SAV. Forexample, the IMD 16 can easily adjust the AV delay (whetheratrial-sensed or atrial-paced) according to the detected currentcycle-length. Referring briefly to Table 3, cycle length 750 mscorresponds to a PAV of 180 ms and a SAV of 160 ms. Accordingly, the PAVcan be adjusted or the SAV can be adjusted to the designated optimumlevels.

Table 3 is automatically generated by the programmer 24 and stored intomemory. Programmer 24, for example, can initiate atrial pacing atdifferent rates. The optimal PAV can be determined and stored intomemory for a given atrial pacing rate. The corresponding optimal SAV canbe determined for the same rate by subtracting ΔAV_(rest) as previouslydiscussed and storing the optimal SAV value for that rate.

Table 3 is a look-up table of optimal PAV and SAV for differentcycle-lengths from resting (1000 ms) to upper tracking rate (500 ms)

Cycle length (CL) Optimum PAV Optimum SAV (ms) (ms) (ms) 1000 180 140950 180 140 900 160 120 850 160 120 800 160 120 750 160 120 700 160 120650 140 100 600 140 100 550 120 80 500 120 80

While the invention has been described in its presently preferred form,it will be understood that the invention is capable of modificationwithout departing from the spirit of the invention as set forth in theappended claims. For example, in one or more embodiments, two or more LVelectrodes may be selected for multi-site pacing of the LV. An exampleof such a configuration may be seen with respect to U.S. Pat. No.6,804,555 issued Oct. 12, 2004, and assigned to the assignee of thepresent invention, the disclosure of which is incorporated by referencein its entirety herein. Moreover, while the electrodes have beendescribed as being able to either sense or pace, skilled artisansappreciate that other embodiments can employ electrodes that are able toboth sense and pace. Additionally, many different medical electricalleads can be used to implement one or more embodiments. For example, StJude's Quartet™ Quadripolar, left-ventricular pacing lead or BostonScientific's EASYTRAK left ventricular pacing/sensing lead can be used.

The techniques described in this disclosure, including those attributedto the IMD 16, the programmer 24, or various constituent components, maybe implemented, at least in part, in hardware, software, firmware, orany combination thereof. For example, various aspects of the techniquesmay be implemented within one or more processors, including one or moremicroprocessors, DSPs, ASICs, FPGAs, or any other equivalent integratedor discrete logic circuitry, as well as any combinations of suchcomponents, embodied in programmers, such as physician or patientprogrammers, stimulators, image processing devices, or other devices.The term “module,” “processor,” or “processing circuitry” may generallyrefer to any of the foregoing logic circuitry, alone or in combinationwith other logic circuitry, or any other equivalent circuitry.

Such hardware, software, and/or firmware may be implemented within thesame device or within separate devices to support the various operationsand functions described in this disclosure. In addition, any of thedescribed units, modules, or components may be implemented together orseparately as discrete but interoperable logic devices. Depiction ofdifferent features as modules or units is intended to highlightdifferent functional aspects and does not necessarily imply that suchmodules or units must be realized by separate hardware or softwarecomponents. Rather, functionality associated with one or more modules orunits may be performed by separate hardware or software components, orintegrated within common or separate hardware or software components.

Skilled artisans also appreciate that the exemplary methods presented inthe flow diagrams are intended to illustrate the general functionaloperation of the devices described herein, and should not be construedas reflective of a specific form of software or hardware necessary topractice all of the methods described herein. It is believed that theparticular form of software will be determined primarily by theparticular system architecture employed in the device (e.g., IMD 16,programmer 24) and by the particular detection and therapy deliverymethodologies employed by the device and/or system. Providing softwareand/or hardware to accomplish the described methods in the context ofany modern IMD or programmer, given the disclosure herein, is within theabilities of one of skill in the art.

When implemented in software, the functionality ascribed to the systems,devices and techniques described in this disclosure may be embodied asinstructions on a computer-readable medium such as RAM, ROM, NVRAM,EEPROM, FLASH memory, magnetic data storage media, optical data storagemedia, or the like. The instructions may be executed by one or moreprocessors to support one or more aspects of the functionality describedin this disclosure. It is appreciated that the LV electrodes can beplaced at locations about and/or along the LV. It is also appreciatedthat more than four LV electrodes can be used to monitor electricalactivation times.

Furthermore, it is understood that FI is a function of multiplevariables such as pacing electrode, A-V delay. Optimization of FI isbased on any one variable while keeping the other variables at aconstant value. Additionally, other embodiments are contemplated inwhich a physician may optionally perform one or more operations for anymethods described herein.

This disclosure has been provided with reference to illustrativeembodiments and is not meant to be construed in a limiting sense. Asdescribed previously, one skilled in the art will recognize that othervarious illustrative applications may use the techniques as describedherein to take advantage of the beneficial characteristics of theapparatus and methods described herein. For example, it is contemplatedthat other embodiments could use electrodes that are configured to paceand sense. Various modifications of the illustrative embodiments, aswell as additional embodiments of the disclosure, will be apparent uponreference to this description.

What is claimed:
 1. A method of cardiac pacing employing a plurality ofleft ventricular electrodes, comprising: a) pacing in a first fusionpacing configuration using a first one of the left ventricularelectrodes and measuring activation times at other ones of the leftventricular electrodes and one or more right ventricular electrodes; b)pacing in a second fusion pacing configuration using a second one of theleft ventricular electrodes and measuring activation times at othernon-pacing ones of the left ventricular electrodes and one or more rightventricular electrodes; and c) employing weighted sums of the measuredactivation times in left and right ventricles during pacing to determinea fusion index (FI) and select one of the left ventricular electrodesfor delivery of subsequent pacing pulses, the weighted sums employingeach electrode's physical distance from the pacing electrode, whereineach sum being a weighted sum of the activation times measured atrespective non-pacing left ventricular electrodes during a respectivefusion pacing.
 2. The method of claim 1 wherein the weighted sums ofmeasured activation times include a weighting factor associated with theelectrode of the left ventricular electrodes and another weightingfactor associated with each electrode of the one or more RV electrodes,each weighting factor is based on each electrode's distance from thepacing electrode.
 3. The method of claim 2 wherein a summation of eachweighting factor associated with each electrode of the left ventricularelectrodes and another weighting factor with each electrode of the oneor more RV electrodes is
 1. 4. The method of claim 1, further comprisingdetermining whether the first one or the second one of the leftventricular electrodes has a lowest measured activation time duringbaseline rhythm where baseline rhythm may comprise one of intrinsicatrioventricular rhythm or right ventricular only pacing.
 5. The methodof claim 4, further comprising determining a first FI associated withthe first one and a second FI for the second one.
 6. The method of claim5, further comprising determining which left ventricular electrodeproduces a lesser FI during fusion pacing.
 7. The method of claim 6wherein selecting one of the left ventricular electrodes is based uponthe lesser FI.
 8. The method of claim 7 further comprising comparing aFI for each of the left ventricular electrodes.
 9. The method of claim 7further comprising sorting the FI for each of the left ventricularelectrodes.
 10. The method of claim 7 further comprising: determining ΔTof fusion index; and selecting one of the left ventricular electrodesfor delivery of subsequent pacing pulses based upon ΔT ms of a minimumFI.
 11. The method of claim 10 wherein ΔT is about 10 milliseconds orless.
 12. The method of claim 7 wherein the left ventricular electrodesexhibit about an equivalent FI; and ΔT is about 15 milliseconds or less.13. The method of claim 7 wherein ΔT is about 5-15 milliseconds.
 14. Themethod of claim 7 further comprising selecting two or more leftventricular electrodes from which to pace.
 15. The method of claim 1,further comprising selecting one or more of the left ventricularelectrodes for delivery of subsequent pacing pulses.
 16. The method ofclaim 1 wherein a left ventricular quadripolar lead is employed.
 17. Themethod of claim 1 wherein a left ventricular quadripolar lead includes aleft ventricular electrode spaced about 1.5 millimeters away fromanother left ventricular electrode.
 18. The method of claim 1, whereinthe weighted fusion index is determined through a weighted fusion indexequation (“FI(j,A)” defined as:FI(j,A)=Σ_(i=1) ^(n) w _(LV)(i,j)|LVAT(i,A|)+Σ_(i=1) ^(m) w_(RV)(i,j)|RVAT(i,A|) wherein factor w(i, j) is based on a distance of anon-pacing electrode i from a pacing electrode j, “A” is anatrio-ventricular delay between atrial sense or pace and a ventricularpacing pulse, “n” is the total number of left ventricular (LV)electrodes, m is a total number of right ventricular (RV) electrodes, LVelectrical activation times (“LVAT(i, A)”) at each non-pacing LVelectrode denoted by i and RV electrical activation times RVAT(i, A) ateach RV electrode i.
 19. The method of claim 1, wherein the weightedfusion index is determined through a weighted fusion index equation thatdepends on weighting factors that are based on a distance of anon-pacing electrode i from a pacing electrode j, an atrio-ventriculardelay between an atrial sense or pace and a ventricular pacing pulse, atotal number of left ventricular (LV) electrodes, a total number ofright ventricular (RV) electrodes, LV electrical activation times ateach non-pacing LV electrode and RV electrical activation times at eachRV electrode.
 20. A system of fusion pacing employing a plurality ofleft ventricular electrodes, comprising: a) means for pacing in a firstfusion pacing configuration using a first one of the left ventricularelectrode and measuring activation times at other ones of the leftventricular electrodes and one or more right ventricular electrodes; andb) means for pacing in a second fusion pacing configuration using asecond one of the left ventricular electrodes and measuring activationtimes at other non-pacing ones of the left ventricular electrodes andone or more right ventricular electrodes; and c) means for employingweighted sums of the measured activation times in left and rightventricles during pacing to determine a fusion index(FI) and select oneof the ventricular electrodes for delivery of subsequent pacing pulses,the weight sums employing each electrode's physical distance from thepacing electrode, wherein each sum being a weighted sum of theactivation times measured at respective non-pacing left ventricularelectrode during a respective fusion pacing.
 21. The system of claim 20,further comprising: means for determining whether the first one or thesecond one of the ventricular electrodes has a lowest weighted sum ofmeasured activation times during pacing.
 22. The system of claim 21,further comprising: means for determining a first fusion index (FI)associated with the first one of the ventricular electrodes and a secondFI for the second one of the ventricular electrodes.
 23. The system ofclaim 22, further comprising: means for determining which ventricularelectrode produces a lesser FI during fusion pacing.
 24. The system ofclaim 21, wherein a ventricular medical electrical lead includessubstantially equally spaced ventricular electrodes.
 25. The system ofclaim 21, wherein a ventricular medical electrical lead includes atleast two closely spaced ventricular electrodes.
 26. The system of claim25, wherein the at least two closely spaced ventricular electrodes arewithin 1.5 mm.
 27. The system of claim 20, further comprising: means forselecting one or more of the ventricular electrodes for delivery ofsubsequent pacing pulses.
 28. The system of claim 27 wherein selectingone of the ventricular electrodes is based upon the lesser FI.
 29. Thesystem of claim 28 further comprising: means for comparing a FI for eachof the ventricular electrodes.
 30. The system of claim 28 furthercomprising: means for determining ΔT of fusion index; and means forselecting one of the ventricular electrodes for delivery of subsequentpacing pulses based upon AT ms of a minimum FI.
 31. The system of claim28 wherein the ventricular electrodes exhibit about an equivalent FI;and ΔT is about 15 ms or less.
 32. The system of claim 28 furthercomprising: means for selecting a ventricular electrode for delivery ofsubsequent pacing pulses from among a set of electrodes with equivalentFI values, based on which of them has the latest activation time duringbaseline rhythm.
 33. The system of claim 28 further comprising selectingtwo or more ventricular electrodes from which to pace.
 34. The system ofclaim 20 further comprising: means for sorting the FI for each of theventricular electrodes.
 35. The system of claim 20 wherein a ventricularquadripolar lead is employed, the ventricular quadripolar lead includessubstantially equally spaced ventricular electrodes.
 36. Anon-transitory machine readable medium containing executable computerprogram instructions which when executed by a data processing systemcause the system to perform a method of cardiac pacing employing aplurality of left ventricular electrodes, comprising: a) pacing using afirst one of the left ventricular electrodes and measuring activationtimes at other ones of the left ventricular electrodes and one or moreright ventricular electrodes; b) pacing using a second one of the leftventricular electrodes and measuring activation times at other ones ofthe left ventricular electrodes and one or more right ventricularelectrodes; and c) employing weighted sums of the measured activationtimes in the left and right ventricles during pacing to determine afusion index (FI) and to select one of the left ventricular electrodesfor delivery of subsequent pacing pulses, the weighted sums employingeach electrode's physical distance from the pacing electrode, whereineach sum being a weighted sum of the activation times measured atrespective non-pacing left ventricular electrodes during a respectivefusion pacing.